Overcoming primary and acquired erlotinib resistance with epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K) co-inhibition in pancreatic cancer

PI3K/Akt is over-expressed in 50-70% of pancreatic ductal adenocarcinoma (PDAC). The hypothesis of this study is that PI3K and EGFR co-inhibition may be effective in PDAC with upregulated PI3K/Akt/mTOR (PAM) signaling. Five primary PDAC and two erlotinib acquired resistant (ER) cell lines with significantly over-expressed AKT2 gene, total Akt and pAkt, were used. Multiple inhibitors of the MAPK and PAM were tested alone or in combination by western blotting, cell proliferation, cell cycle, clonogenic, apoptosis, and migration assays. Erlotinib acted synergistically with PI3Kα inhibitor BYL in both ER cell lines (synergy index, SI=1.71 and 1.44 respectively). Treatment of ER cell lines by this dual blockade caused significant G1 cell cycle arrest (71%, P<0.001; 58%, P=0.003), inhibition of colony formation (69% and 72%, both P<0.001), and necrosis and apoptosis (75% and 53%, both P<0.001), more so compared to parent cell lines. In primary patient-derived tumor subrenal capsule (n=90) and subcutaneous (n=22) xenografts, Erlotinib plus BYL significantly reduced tumor volume (P=0.005). Strong pEGFR and pAkt immunostaining (2+/3+) was correlated with high response to erlotinib and low response to erlotinib plus BYL respectively. In conclusion, PDAC with increased expression of the PAM signaling were susceptible to PI3K/ EGFR co-inhibition suggesting oncogenic dependence. Erlotinib plus BYL should be considered for a clinical study in PDAC; further evaluation of pEGFR and pAkt expression as potential predictive biomarkers is warranted

Fragility curves for buildings in Hong Kong

Fragility curves are the tools for evaluating the damage of structural or nonstructural components under different levels of ground excitation. It is also the necessary information for calculating the life-cycle cost of buildings during their design period. In this paper, development of fragility curves for buildings designed based on HK standard is presented. Two prototype models, which include three-storey and tenstorey reinforced concrete rigid frames, were considered. Incremental dynamic analysis was conducted under nine sets of past earthquake records with scaled peak ground accelerations. Maximum inter-storey drift ratio was selected as the damage indices and three performance levels were considered. Based on the numerical results, two fragility curves were developed to quantify the damage probability of RC buildings with different building heights

Revitalizing the moment distribution method: A fast and exact analysis of multibay, multi-story frames.

The conventional moment distribution method is revitalized with a new approach which requires only one-cycle of balance and carry-over and no iteration. For a continuous beam, the method begins by assuming the value of the balancing moment, say x, at the first joint. By invoking the moment equilibrium condition successively from the first towards the last joints, balancing and carry-over moments at other joints can be determined in terms of the unknown x without iteration. By means of moment equilibrium of the last joint, the unknown x can be solved exactly, regardless of the number of spans, and the final moment distribution of the whole structure can be easily obtained. Further, for multi-bay, single story frames, the analysis is carried out without the need to separate the analysis into two stages as in conventional MDM, and the final exact moments are found by solving two unknowns only, regardless of the number of bays. As such, the revitalized MDM is particularly advantageous for solving continuous beams and single-story frames with large number of spans or bays. Five examples are given herein to demonstrate the procedures and efficiency of the proposed method

Seismic behavior of non seismically designed eccentric reinforced concrete beam column joints

Non seismically designed eccentric reinforced concrete beam column joints were extensively used in existing reinforced concrete frame buildings, which were found to be vulnerable to seismic action in many incidences. To provide a fundamental understanding of the seismic performance and failure mechanism of the joints, three 2/3 scale exterior beam column joints with non seismically designed details were cast and tested under reversed cyclic loads simulating earthquake excitation. In this investigation, particular emphasis was given on the effects of the eccentricity between the centerlines of the beam and the column. It is shown that the eccentricity had significant effects on the damage characteristics, shear strength, and displacement ductility of the specimens. In addition, shear deformation and the strain of joint hoops were found to concentrate on the eccentric face of the joint. The results demonstrated that the specimen with an eccentricity of 1/4 column width failed in a brittle manner with premature joint shear failure, while the other specimens with less or no eccentricity failed in a ductile manner with joint shear failure after beam flexural yielding. Test results are compared with those predicted by three seismic design codes and two non seismic design codes. In general, the codes do not accurately predict the shear strength of the eccentric joints with non seismic details

Effects of beam-column depth ratio on seismic behaviour of non-seismic detailed reinforced concrete beam-column joints

Four reinforced concrete exterior beam-column joints with open anchorage beam reinforcement, which are manufactured to simulate those in existing reinforced concrete framed buildings, are tested under reversed cyclic loads simulating earthquake excitation. The particular emphasis of this project is given to the effects of the beam-column depth ratio and the stirrup ratio in joints on the shear strength and seismic behaviour of the exterior joints without seismically designed details. The experimental results indicate that the stirrup placed in the beam-column joint cores can effectively improve the shear strength of the joint and enhance the seismic performance, and the shear strength of the joints decreases when the beam-column depth ratio increases. The experimental results are also compared with the results predicted by two non-seismic design codes (Eurocode 2 and HK code 2013) and three codes for seismic design (Eurocode 8, ACI 318-14 and NZS 3101). In general, the current non-seismic design codes and seismic design codes of practice cannot accurately predict the shear strength of the exterior joints with non-seismically designed details. It is shown that neglecting the seismic design of beam-column joints may lead to potential damage of reinforced concrete framed buildings in unexpected moderate or low seismic areas

Effects of eccentricity on seismic behavior of non-seismically designed reinforced concrete beam-column joint

The staggering numbers of eccentric reinforced concrete beam-column joints without seismic design details were used in existing RC frame building due to geometrical constraints, which implied high susceptibility of the building structures to anticipated seismic risk. Three exterior RC beam-column joints were fabricated and tested, which were applied reversed cyclic loads to simulate seismic action. In this study, the effects of stirrup ratio in joints and the eccentricity which is defined as the distance between the axis of the beam and column on seismic performance are investigated. The test results provide a further understanding of the failure mode and shear strength of exterior beam-column joints. It is shown that the eccentricity will significantly reduce the seismic performance and shear strength of the joints, which will cause the brittle failure of frame buildings, while the stirrups in the joint core can improve the seismic performance. To verify the availability of current codes in predicting the shear strength of eccentric beam-column joints with non-seismic detailed, the experimental results are compared with the predicted shear force of two nonseismic codes (HK code and Eurocode 2) and three seismic codes (Eurocode 8, NZS 3101 and ACI 318-14). The comparison results indicate that the existing non-seismic and seismic design codes of practice do not predict the shear strength of the exterior non-seismically designed joints precisely

Biorefining Waste Sludge From Water and Sewage Treatment Plants Into Eco-Construction Material

This study aims to investigate the feasibility of using different waste sludge and coal combustion residuals in eco-concrete block production. The compressive strength of the eco-concrete blocks produced by waterworks sludge, bottom and fly ashes were 36 MPa, which comply with the standard specifications for paving blocks in Hong Kong. The optimal mixing proportion (by weight) of different materials in the blocks, such as aggregates, cementitious materials, water, and fly ash was 1.1:1.0:0.5:0.22, respectively. The environmental and toxicological impacts of the final products were then evaluated according to the toxicity characteristic leaching procedure (TCLP). While several heavy metals (i.e., Hg, Cu, and Pb) have been identified in the specimens, the levels of these contaminants complied with Standards (US 40 CFR 268.48). Waste materials generated from water and sewage treatment processes and power plants are feasible to be used as ingredients for paving concrete block production. These products are environmentally acceptable and mechanically suitable for resource recovery of waste materials

Parenting approaches, family functionality, and internet addiction among Hong Kong adolescents

© 2016 Wu et al. Background: Internet addiction (IA) among adolescents has become a global health problem, and public awareness of it is increasing. Many IA risk factors relate to parents and the family environment. This study examined the relationship between IA and parenting approaches and family functionality. Methods: A cross-sectional study was conducted with 2021 secondary students to identify the prevalence of IA and to explore the association between adolescent IA and familial variables, including parents' marital status, family income, family conflict, family functionality, and parenting approaches. Results: The results revealed that 25.3 % of the adolescent respondents exhibited IA, and logistic regression positively predicted the IA of adolescents from divorced families, low-income families, families in which family conflict existed, and severely dysfunctional families. Interestingly, adolescents with restricted Internet use were almost 1.9 times more likely to have IA than those whose use was not restricted. Conclusions: Internet addiction is common among Chinese adolescents in Hong Kong, and family-based prevention strategies should be aligned with the risk factors of IA.Link_to_subscribed_fulltex